ENANTIOSELECTIVE CONJUGATE ADDITION OF GRIGNARD-REAGENTS TO ENONES CATALYZED BY CHIRAL CUPRATE COMPLEXES

The enantioselective conjugate addition of Grignard reagents to enones catalyzed by copper(I) complexes with bidentate chiral auxiliary ligands, N,Nʹ-dlalkyl-substituted aminotropone iminates, 2 and 3, has been studied. The enantioselectivity of the reaction was significantly increased by addition of HMPA and silyl reagents. In the reaction of n-BuMgCl and 2-cyclohexen-1-one, Cu(R-CHIRAMT) (0.05 mol per mol equiv of 2-cyclohexen-1-one) prepared in situ catalyzed the conjugate addition to give (S)-3-butylcyclohexanone with 20% enantiomeric excess (ee). In the presence of HMPA and a bulky silyl reagent, Ph2(t-Bu)SiCl, however, the reaction afforded (S)-3-butylcyclohexanone with a 74% ee. Under stoichiometric conditions, the product was obtained in 78% ee. Limitations on the scope of the enantioselectivity afforded by the Cu(R-CHIRAMT) catalyst were revealed by studies with a variety of Grignard reagent and enones. In these cases, however, the regioselectivity of the catalyst remained high. In the conjugate addition of vinylmagnesium bromide to (S)-4-[dimethyl(1ʹ,1ʹ-dimethylethyl)slloxy]-2-cyclopentenone, 4, Cu(S-CHIRAMT) catalyzed the reaction 5.6 times faster than Cu(R-CHIRAMT), indicating that these chiral catalysts might be useful for the kinetic resolution of racemic mixtures of 4, an important precursor in prostaglandin synthesis. © 1990, American Chemical Society. All rights reserved.